Polymer micelles are one of widely used drug delivery systems (DDSs) for solubilizing various poorly soluble drugs such as a large portion of anticancer drugs, and also for delivery of the drug to the target site. Usually, block copolymers, composed of water-soluble polyethylene glycol (PEG) and water-insoluble polymer, are utilized to form polymer micelles, providing a hydrophilic outer shell and a hydrophobic inner core. The poorly soluble drugs are encapsulated in the latter via hydrophobic interaction with the hydrophobic portion of the copolymer and stay within the hydrophilic outer shell. As for PEG-based block copolymer micelles, poly(amino acid) complex of PEG-based copolymers such as PEG-block-poly(α,β-aspartic acid) and PEG-block-poly(L-lysine) are reported as remarkable functional materials for DDS.
Recently, hydrotropic compounds are drawing attention as useful compounds for improving solubility of the hydrophobic drugs. It was previously reported that diethylnicotinamide was identified to improve the solubility of paclitaxel in a dose depending manner from a screening for over 60 commercially available hydrotropes (Kinam et al., Pharmaceutical Research, Vol. 20, 2003, 1022-1030). After this report, the same author further reported that PEG-based block copolymers bearing diethylnicotinamide (DENA) and dimethylbenzamide (DMBA) moiety were able to encapsulate paclitaxel (Kinam etal., Journal of Controlled Release, Vol. 152, 2011, 13-20). Further, it has been reported that DENA was a hydrotropic agent for paclitaxel and improved a release profile of paclitaxel in poly(lactic-co-glycolic acid) (PLGA) matrices (Baek et al., J. Biomater. Sci. Polymer Edn, Vol. 15, No. 4, pp. 527-542 (2004)).